Regulation of differentiation and reproduction of vascular organs by Edg receptor expression
| Project/Area Number |
15590064
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Nagoya City University |
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Principal Investigator |
MURAKI Katsuhiko Nagoya City University, Graduate school of Pharmaceutical Sciences, Associate Professor, 大学院・薬学研究科, 助教授 (20254310)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | lipid mediator / calcium / ion channel / cell differentiation / cell proliferation / スフィンゴシン1燐酸 / 血管平滑筋 / フェノタイプ / ヒト血管内皮細胞 / 分化・細胞増殖 / カチオンチャネル |
|---|
| Research Abstract |
Objective: Palmitoyl-L-carnitine (palcar), which accumulates in ischemic heart, affects cellular functions of vascular endothelium in the ischemic area. The aim of the study was to examine the effects of palcar on intracellular Cat^<2+> concentration ([Ca^<2+>]i) in vascular endothelial cells in comparison with those of sphingosine-1-phosphate (S1P) and to investigate the underlying mechanisms. Methods and Results: Human umbilical vein endothelial cells (huvecs) were loaded with Fura-2 AM and the fluorescence signal was measured with Argus 50/CA imaging system. Application of palcar at a concentration range between 0.3 and 3μM elevated [Ca^<2+>]i i in huvecs and its potency was about 30 times lower than that of S1P. Although the sensitivity to palcar and S1P varied widely among huvecs from individuals, response to 3 μM palcar in each huvec clearly paralleled that to 0.3 μM S1P (r=0.79, P<0.001). In addition, huvecs that were treated with 100 ng/ml pertussis toxin (PTX) for 15 hr failed to respond to palcar as well as to S1P, but did respond to 3 μM His. On the other hand, pre-treatment of huvecs with palcar abolished subsequent S1P-induced elevation of [Ca^<2+>]i, but not the His-induced elevation. Conclusions: Our data indicate that palcar has a novel action on huvecs as a potential agonist of receptors for S1P. Effective inhibition of response to S1P by palcar suggests that palcar affects angiogenesis regulated by S1P.
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Report
(3 results)
Research Products
(22 results)
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[Journal Article] Modified cardiovascular L-type channels in mice lacking the voltage-dependent Ca^<2+> chanel β3 subunit2003
Author(s)
Manabu Murakami, Hisao Yamamura, Takashi Suzuki, Myoung-Goo Kang, Susumu Ohya, Agnieszka Murakami, Ichiro Miyoshi, Hironobu Sasano, Katsuhiko Muraki, Takuzo Hano, Noriyuki Kasai, Shinsuke Nakayama, Kevin P. Campbell, Veit Flockerzi, Yuji Imaizumi, Teruyuki Yanagisawa, Toshihiko Iijima
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Journal Title
J. Biol. Chem. 278
Pages: 43261-43267
Description
「研究成果報告書概要(欧文)」より
Related Report
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